Scientists peek inside healthy brains to find the cause of Alzheimer's: Experimental new treatment will scan 'tangles' in nerve cells that may trigger disease

Wednesday 27th, May 2015 |
News

Scientists are scanning the brains of healthy elderly citizens as part of an ambitious new Alzheimer's treatment which hopes to discover the cause of the disease. Previous research has identified two hallmarks of Alzheimer's - sticky brain plaque and tangles of a protein named tau that clog dying brain cells. Using the latest technology, experts can now spot these tangles in living brains - and they hope that extensive scanning of healthy subjects will provide clues to what triggers the debilitating disease.

Previous research highlights sticky brain plaque as hallmark of disease

Another common sign is tangles of protein named tau that clog brain cells

The tau brain scans will be added to a new study in the U.S. that's testing if an experimental drug might help healthy but at-risk people stave off Alzheimer's. Whether that medication works or not, it's the first drug study where scientists can track how both of Alzheimer's signature markers begin building up in older adults before memory ever slips. 'The combination of amyloid and tau is really the toxic duo - to see it in life is really striking,' said Dr. Reisa Sperling of Boston's Brigham and Women's Hospital and Harvard Medical School, who is leading the so-called A4 study, which is enrolling participants in the U.S., Australia and Canada.

More than 35 million people worldwide have Alzheimer's or similar dementias. Those numbers are expected to rise rapidly as the baby boomers get older. There is no good treatment. Today's medications only temporarily ease symptoms and attempts at new drugs, mostly targeted at sticky amyloid, have failed in recent years. Some believe treatment needs to start at an earlier stage. Scientists now think Alzheimer's begins quietly ravaging the brain more than a decade before symptoms appear, much like heart disease is triggered by gradual cholesterol buildup. Brain scans show many healthy older adults quietly harbour those sticky amyloid plaques, not a guarantee that they'll eventually get Alzheimer's but an increased risk. Yet more recent research, including a large autopsy study from the Mayo Clinic, suggests that Alzheimer's other bad actor - that tangle-forming tau protein - also plays a big role.

The newest theory is that Amyloid sparks a smoldering risk, but later spread of toxic tau speeds the brain destruction. Normal tau acts sort of like railroad tracks to help nerve cells transport food and other molecules. But in Alzheimer's, the protein's strands collapse into tangles and eventually the cell dies. According to Dr Sperling, most healthy people have a small amount of dysfunctional tau in one part of the brain by their 70s. But amyloid plaques somehow encourage this bad tau to spread toward the brain's memory centre, she explained.

The A4 study may give some clues. The goal is to check up to 500 people for tau three times over the three-year study, as researchers tease out when and how it forms in those who are still healthy. They won't be told the results - scientists don't know enough yet about what the scans portend. At the same time, study participants will receive either an experimental anti-amyloid drug - Eli Lilly & Co.'s solanezumab - or a placebo as researchers track their memory.

The £90million study is funded by the National Institutes of Health, Lilly and others; the Alzheimer's Association helped fund the addition of the tau scans. The idea: If the drug proves to be helpful, it might be tamping down amyloid formation that in turn reins in toxic tau. In previous studies, solanezumab failed to help full-blown Alzheimer's but appeared to slow mental decline in patients with mild disease, raising interest in testing the still healthy.